Switching to Anti-VEGF Agents for Anatomical Rescue for Bevacizumab Nonresponders: Study

While anti-VEGF therapy is the standard for DME and nAMD, managing nonresponders with persistent fluid remains a clinical challenge due to a lack of controlled evidence on drug switching. Dr. Rotem Gindelskhi Sagiv and colleagues from Kaplan Medical Center and the Hebrew University of Jerusalem. addressed this gap by comparing therapeutic rotation against continued bevacizumab in patients with suboptimal initial responses.

Therefore, the retrospective analysis of 59 eyes failing bevacizumab therapy (<10% CMT reduction after 3–6 injections) compared switching to aflibercept or ranibizumab against a bevacizumab control. Excluding eyes with vitreous hemorrhage or prior outside treatment, the study assessed CMT change as the primary endpoint and visual acuity as the secondary outcome.

Key Clinical Findings of the Study Include:

• Significant cohort-wide anatomical gains: The study demonstrated that switching to a second-line agent resulted in a significant 82.1-micron decrease in mean CMT (P < 0.001), whereas the control group showed no significant change.

• Superiority in neovascular age-related macular degeneration (nAMD): For patients with nAMD, switching agents was statistically superior to continuing bevacizumab (P = 0.025), with switchers achieving a 92.6-micron CMT reduction compared to just 5.71 microns in the continuation group.

• DME anatomical response trends: In diabetic macular edema (DME), switchers saw a significant CMT decrease of 38.5 microns (P = 0.01), though the difference when compared directly to the bevacizumab control group did not reach statistical significance (P = 0.22).

• Functional stability across groups: Despite the clear structural improvements, the study found no significant difference in visual acuity between those who switched and those who continued bevacizumab, highlighting a dissociation between anatomical and functional recovery.

The results suggest that switching anti-VEGF agents is anatomically beneficial for nonresponding eyes, as switchers in the total cohort achieved a significant CMT reduction to 369.21 microns while the continuation group remained largely unchanged at 406.40 microns. These findings indicate that clinicians may find therapeutic rotation a valuable strategy for managing persistent retinal fluid in eyes that show a suboptimal initial response to bevacizumab.

The study's retrospective design and relatively small population mean that while the anatomical benefits are clear, the long-term functional impact and the need for larger prospective trials with control groups remain essential areas for future research.

Reference

Sagiv RG, Rosenblatt HN, Zamir E, Altarescu A, Ben-Zaken SG, Rotfogel Z. Efficiency of anti-vascular endothelial growth factor drug switch in patients who did not respond to a series of bevacizumab injections. Indian J Ophthalmol 2026;74:777-83.